The red imported fire ant, Solenopsis invicta Buren (Hymenoptera: Formicidae), is an invasive pest affecting urban and rural communities, agricultural production and wildlife. Its complex biology and genetics is reflected in the existence of two different colony forms: monogyne and polygyne. We focus our studies on the polygyne form more abundant in Texas, characterized by the presence of multiple queens that co-operate for colony success. Our conceptual framework resides in the hypothesis that understanding gene networks linking nutrition and reproduction may reveal critical signaling pathways that could be disrupted to manage fire ants. In the pre-omics era we began by systematically cloning and characterizing the expression of genes and proteins important for reproduction and signaling and that we believe participate in the fire ant ‘genetic tool kit’. Our earlier studies focused on the vitellogenin receptor (VgR) and in the application of RNAi to reduce VgR gene expression as proof of principle that gene silencing in queens could lead to impaired egg production. Signaling systems related to reproduction and nutrition were also studied, such as the insulin receptors and the sNPF receptor, a G protein-coupled receptor. We have immunolocalized the sNPF receptor in the brain of queens and workers and found correlations in its neuronal gene expression in both castes with respect to the presence or absence of brood in the colony. We have generated and compared transcriptomes of mated and virgin queen brains and ovaries and identified a few differentially expressed genes. Most recently, with the release of the new fire ant genome in the Fall of 2018, we mined the genome to compile and curate the annotation of G protein-coupled receptors. The lecture will summarize key aspects of the biology of fire ants and morphological and functional differences among colony members. Experimental approaches utilized to begin to understand regulation of colony growth at the molecular level will be presented. It is our goal to unravel the endocrinological control of the fire ant colony with the hope of identifying novel targets to impair queen maturation, ovarian development, colony nutrition and brood production.